A liposome-based sustained-release delivery system for i.m. injection of water-soluble drugs is proposed. Gentamicin will be used to validate the concept. Objectives include preparation of liposomes with a wide range of release rates in serum (in vitro), selection of suitable compositions for pharmacokinetic evaluation in vivo (mice), monitoring of removal of lipids from the injection site (gamma-scintigraphy), and histological inspection of the injection site. Prolonged sub-toxic gentamicin plasma levels, and therefore reduced side-effects (improved Therapeutic Index), and reduction of frequency of administration (cost reduction, improved patient compliance) are expected to result from such a delivery system. In Phase II, pharmacokinetic studies will be expanded to efficacy and toxicity studies in animals to assess improvement of the Therapeutic Index. Also production of liter-size quantities of sterile, pyrogen-free liposomes will be initiated to support animal studies and eventually clinical trials. Non-toxic, biocompatible parenteral depot carrier systems are currently not available. Therefore, innovative development of numerous novel drug/carrier compounds can be expected on the basis of the results of this project.